1. Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients
Joachim Struck, Andreas Bergmann, Chen Tao, Nils G Morgenthaler Peptides . 2004 Aug;25(8):1369-72. doi: 10.1016/j.peptides.2004.06.019.
Adrenomedullin and PAMP are potent vasodilatory peptides derived from a common larger precursor peptide. Elevation of circulating levels of both peptides has been described for diseases involving dysfunction of the cardiovascular system. However, the reliable quantification has been hampered by their short half-life times and - as known for Adrenomedullin -- the existence of a binding protein. Here we report the identification of another peptide derived from the Adrenomedullin precursor, termed proADM 45-92, which is present in large concentrations in plasma of septic shock patients. This peptide is produced in stoichiometric amounts to Adrenomedullin and PAMP, but -- contrary to them -- is apparently non-functional and stable. Thus, proADM 45-92 represents a suitable diagnostic target which could be used to assess the concentrations of Adrenomedullin gene products released into the bloodstream.
2. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay
Joachim Struck, Andreas Bergmann, Christine Alonso, Nils G Morgenthaler Clin Chem . 2005 Oct;51(10):1823-9. doi: 10.1373/clinchem.2005.051110.
Background:Adrenomedullin (ADM) is a potent vasodilatory peptide, and circulating concentrations have been described for several disease states, including dysfunction of the cardiovascular system and sepsis. Reliable quantification has been hampered by the short half-life, the existence of a binding protein, and physical properties. Here we report the technical evaluation of an assay for midregional pro-ADM (MR-proADM) that does not have these problems.Methods:MR-proADM was measured in a sandwich immunoluminometric assay using 2 polyclonal antibodies to amino acids 45-92 of proADM. The reference interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147 female), and increased MR-proADM concentrations were found in 95 patients with sepsis and 54 patients with cardiovascular disease.Results:The assay has an analytical detection limit of 0.08 nmol/L, and the interassay CV was 0.12 nmol/L. The assay was linear on dilution with undisturbed recovery of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20% loss of analyte) for at least 3 days at room temperature, 14 days at 4 degrees C, and 1 year at -20 degrees C. MR-proADM values followed a gaussian distribution in healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10-0.64 nmol/L), without significant difference between males or females. The correlation coefficient for MR-proADM vs age was 0.50 (P < 0.001). MR-proADM was significantly (P < 0.001) increased in patients with cardiovascular disease [median (range), 0.56 (0.08-3.9) nmol/L] and patients with sepsis [3.7 (0.72-25.4) nmol/L].Conclusions:MR-proADM is stable in plasma of healthy individuals and patients. MR-proADM measurements may be useful for evaluating patients with sepsis, systemic inflammation, or heart failure.
3. Influence of confounding factors on plasma mid-regional pro-adrenomedullin and mid-regional pro-A-type natriuretic peptide concentrations in healthy individuals
L L Ng, J Struck, J E Davies, Sanjay S Bhandari Biomarkers . 2011 May;16(3):281-7. doi: 10.3109/1354750X.2011.553750.
Background:MRproADM and MRproANP can be used as diagnostic and prognostic markers in heart failure.Aim:The objective was to identify confounding factors for the interpretation of plasma MRproADM and MRproANP concentrations.Methods:A total of 518 healthy volunteers with a mean age of 60.84 ± 7.41 years were analyzed. We evaluated the influence of demographic factors, renal function and echocardiographic indices on the candidate peptides.Results:Multivariate analysis revealed that age (P < 0.001), BMI (P < 0.001) and eGFR (P < 0.001) were independent predictors for MRproADM concentrations in healthy subjects. The independent predictors for MRproANP were age (P < 0.001), female gender (P < 0.001), heart rate (P < 0.001) and eGFR (P = 0.039).Conclusion:The interpretation of both peptides is multifaceted due to confounders. Knowledge of these factors will further our understanding of how these peptides behave in health and in disease.